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molecular inflammation

M-D Yu, B-H Su, X-X Zhang
OBJECTIVE: To monitor morphological feature and related osteogenic and bone metabolic change during healing of tibia fracture in a rat model. MATERIALS AND METHODS: Tibia density and trabecular thickness were evaluated. Histopathology was examined by HE staining. Serous inflammatory factors IL-4, IL-6, TNF-α and metabolic biomarkers ALP, β-CTX, P1NP, were determined by ELISA. The expression of RUNX2, TGF-β1, VEGF-α, BMP-2, BMP-4, and BMP-7 in callus tissue were qualified by RT-PCR...
March 2018: European Review for Medical and Pharmacological Sciences
Anne Rübsam, Sonia Parikh, Patrice E Fort
Diabetic retinopathy is a common complication of diabetes and remains the leading cause of blindness among the working-age population. For decades, diabetic retinopathy was considered only a microvascular complication, but the retinal microvasculature is intimately associated with and governed by neurons and glia, which are affected even prior to clinically detectable vascular lesions. While progress has been made to improve the vascular alterations, there is still no treatment to counteract the early neuro-glial perturbations in diabetic retinopathy...
March 22, 2018: International Journal of Molecular Sciences
Beatrice Ballarin, Michael Tymianski
Stroke creates a complex interplay of multiple signaing pathways including excitotoxicity, ionic imbalance, inflammation, oxidative stress and apoptosis. There are very few treatments that have been shown to be beneficial in acute stroke. Recent findings have provided insights into the pathophysiology and mechanisms of ischemic stroke, complementing the traditional glutamate hypothesis: the molecular interaction between PSD95 and GluN2B has been identified as a culprit in stroke-mediated excitotoxicity, leading to the discovery of NA-1, a peptide that disrupts that interaction, as a potent neuroprotective agent for the treatment of acute stroke...
March 22, 2018: Acta Pharmacologica Sinica
Avneet Kaur, Sharad Wakode, Dharam Pal Pathak, Vidushi Sharma, Ashok K Shakya
BACKGROUND: Non-steroidal anti-inflammatory drugs are widely used for many years, but the chronic use of NSAID's leads to gastric side effects, ulceration and kidney problems. These side effects are due to non-selective inhibition of COX-2 along with COX-1. Therefore, it is imperative to develop novel and selective COX-2 inhibitors Objective: In this paper wehave synthesized a series of novel hybrids comprising of substituted-N-(3,4,5-trimethoxyphenyl)-benzo[d]oxazole derivatives and screened for the treatment of inflammation...
March 21, 2018: Medicinal Chemistry
Emine Sekerdag, Ihsan Solaroglu, Yasemin Gursoy-Ozdemir
As a result of ischemia or hemorrhage, blood supply to neurons is disrupted which subsequently promotes a cascade of pathophysiological responses resulting in cell loss. Many mechanisms are involved solely or in combination in this disorder including excitotoxicity, mitochondrial death pathways, and the release of free radicals, protein misfolding, apoptosis, necrosis, autophagy and inflammation. Besides neuronal cell loss, damage to and loss of astrocytes as well as injury to white matter contributes also to cerebral injury...
March 20, 2018: Current Neuropharmacology
Michael Koennecke, Ludger Klimek, Joaquim Mullol, Philippe Gevaert, Barbara Wollenberg
Background: Chronic rhinosinusitis (CRS) is a heterogeneous, multifactorial inflammatory disease of the nasal and paranasal mucosa. It has not been possible to date to develop an internationally standardized, uniform classification for this disorder. A phenotype classification according to CRS with (CRSwNP) and without polyposis (CRSsNP) is usually made. However, a large number of studies have shown that there are also different endotypes of CRS within these phenotypes, with different pathophysiologies of chronic inflammation of the nasal mucosa...
2018: Allergo Journal International
Marta Podgórska, Monika Ołdak, Anna Marthaler, Alina Fingerle, Barbara Walch-Rückheim, Stefan Lohse, Cornelia S L Müller, Thomas Vogt, Mart Ustav, Artur Wnorowski, Magdalena Malejczyk, Sławomir Majewski, Sigrun Smola
Persistent genus β-HPV (human papillomavirus) infection is a major co-factor for non-melanoma skin cancer in patients suffering from the inherited skin disease epidermodysplasia verruciformis (EV). Malignant EV lesions are particularly associated with HPV type 5 or 8. There is clinical and molecular evidence that HPV8 actively suppresses epithelial immunosurveillance by interfering with the recruitment of Langerhans cells, which may favor viral persistence. Mechanisms how persistent HPV8 infection promotes the carcinogenic process are, however, less well understood...
2018: Frontiers in Microbiology
Hui Zhou, Meihong Deng, Yingjie Liu, Chenxuan Yang, Rosemary Hoffman, Jingjiao Zhou, Patricia A Loughran, Melanie J Scott, Matthew D Neal, Timothy R Billiar
Thrombocytopenia impairs host defense and hemostasis in sepsis. However, the mechanisms of how platelets regulate host defense are not fully understood. High-mobility group box 1 (HMGB1), a danger-associated molecular pattern protein, is released during infection and contributes to the pathogenesis of sepsis. Platelets express HMGB1, which is released on activation and has been shown to play a critical role in thrombosis, monocyte recruitment, and neutrophil extracellular trap (NET) production. However, the contribution of platelet HMGB1 to host defense is unknown...
March 27, 2018: Blood Advances
Grażyna Janikowska, Tomasz Janikowski, Alina Pyka-Paj K, Urszula Mazurek, Marcin Janikowski, Maciej Gonciarz, Zbigniew Lorenc
BACKGROUNDS: Colorectal cancer is the third most common cancer in economically developed countries. Molecular studies and, in particular, gene expression have contributed to advances in the diagnosis and treatment of many cancers. Genes can be molecular and therapeutic markers, but because of the large molecular diversity in colorectal cancer the knowledge is not yet fully established. Probably one of the most crucial processes during early cancer development is inflammation. The inflammatory response in the tumor is an important indicator of molecular etiology and later of cancer progression...
March 2, 2018: Cancer Biomarkers: Section A of Disease Markers
V N Shishkova, T V Adasheva, A Yu Remenik, V N Valyaeva, V M Shklovsky
AIM: To study the relationship between clinical-anthropometric, biochemical, metabolic, vascular-inflammatory, molecular-genetic parameters and the development of the first ischemic stroke, and to develop a prognostic model for determining the probability of its occurrence. MATERIAL AND METHODS: The study included 196 first ischemic stroke patients and 119 healthy people matched for age, place of residence and nationality to the group of patients. The main anthropometric, clinical, biochemical, metabolic parameters and markers of vascular inflammation and endothelial dysfunction were assessed...
2018: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Lucy P Evans, Elizabeth A Newell, MaryAnn Mahajan, Stephen H Tsang, Polly J Ferguson, Jolonda Mahoney, Christopher D Hue, Edward W Vogel, Barclay Morrison, Ottavio Arancio, Russell Nichols, Alexander G Bassuk, Vinit B Mahajan
Objective: Limited attention has been given to ocular injuries associated with traumatic brain injury (TBI). The retina is an extension of the central nervous system and evaluation of ocular damage may offer a less-invasive approach to gauge TBI severity and response to treatment. We aim to characterize acute changes in the mouse eye after exposure to two different models of TBI to assess the utility of eye damage as a surrogate to brain injury. Methods: A model of blast TBI (bTBI) using a shock tube was compared to a lateral fluid percussion injury model (LFPI) using fluid pressure applied directly to the brain...
March 2018: Annals of Clinical and Translational Neurology
Ponarulselvam Sekar, Duen-Yi Huang, Shwu-Fen Chang, Wan-Wan Lin
Extracellular adenosine 5'-triphosphate (ATP) is a damage-associated molecular pattern and contributes to inflammation associated diseases including cancer. Extracellular acidosis is a novel danger signal in the inflammatory sites, where it can modulate inflammation, immunity and tumor growth. Extracellular acidification was shown to inhibit P2X7-mediated channel currents, while it remains unknown how acidification and P2X7 together affect cellular responses. Here, we treated BV-2 microglial cells with ATP in a short period (<15 min) or a sustained acidified condition...
February 27, 2018: Oncotarget
Petrus Linge, Paul R Fortin, Christian Lood, Anders A Bengtsson, Eric Boilard
Dysregulation of lymphocyte function, accumulation of autoantibodies and defective clearance of circulating immune complexes and apoptotic cells are hallmarks of systemic lupus erythematosus (SLE). Moreover, it is now evident that an intricate interplay between the adaptive and innate immune systems contributes to the pathogenesis of SLE, ultimately resulting in chronic inflammation and organ damage. Platelets circulate in the blood and are chiefly recognized for their role in the prevention of bleeding and promotion of haemostasis; however, accumulating evidence points to a role for platelets in both adaptive and innate immunity...
March 21, 2018: Nature Reviews. Rheumatology
Andrew Kaufman, Ezen Choo, Anna Koh, Robin Dando
Despite evidence that the ability to taste is weakened by obesity and can be rescued with weight loss intervention, few studies have investigated the molecular effects of obesity on the taste system. Taste bud cells undergo continual turnover even in adulthood, exhibiting an average life span of only a few weeks, tightly controlled by a balance of proliferation and cell death. Recent data reveal that an acute inflammation event can alter this balance. We demonstrate that chronic low-grade inflammation brought on by obesity reduces the number of taste buds in gustatory tissues of mice-and is likely the cause of taste dysfunction seen in obese populations-by upsetting this balance of renewal and cell death...
March 2018: PLoS Biology
Céline Hernandez, Peter Huebener, Jean-Philippe Pradere, Daniel J Antoine, Richard A Friedman, Robert F Schwabe
Cell death is a key driver of disease progression and carcinogenesis in chronic liver disease (CLD), highlighted by the well-established clinical correlation between hepatocellular death and risk for the development of cirrhosis and hepatocellular carcinoma (HCC). Moreover, hepatocellular death is sufficient to trigger fibrosis and HCC in mice. However, the pathways through which cell death drives CLD progression remain elusive. Here, we tested the hypothesis that high-mobility group box 1 (HMGB1), a damage-associated molecular pattern (DAMP) with key roles in acute liver injury, may link cell death to injury responses and hepatocarcinogenesis in CLD...
March 20, 2018: Journal of Clinical Investigation
Flora Pirozzi, Kai Ren, Alessandra Murabito, Alessandra Ghigo
Chronic obstructive pulmonary disease (COPD) is a progressive respiratory disorder characterized by irreversible chronic inflammation and airflow obstruction. It affects more than 64 million patients worldwide and it is predicted to become the third cause of death in the industrialized world by 2030. Current available therapies are not able to block disease progression and to reduce mortality, underlying the need of a better understanding of COPD pathophysiological mechanisms to identify new molecular therapeutic targets...
March 20, 2018: Current Medicinal Chemistry
Tanzeel Ur Rehman, Arif-Ullah Khan, Azar Abbas, Javid Hussain, Farman Ullah Khan, Kimberly Stieglitz, Shamsher Ali
In the present study, we describe various pharmacological effects and computational analysis of nepetolide, a tricyclic clerodane-type diterpene, isolated from Nepeta suavis . Nepetolide concentration-dependently (1.0-1000 µg/mL) exhibited 1,1-diphenyl,2-picrylhydrazyl free radical scavenging activity with maximum effect of 87.01 ± 1.85%, indicating its antioxidant potential, as shown by standard drug, ascorbic acid. It was moderately active against bacterial strain of Staphylococcus aureus . In brine shrimp's lethality model, nepetolide potently showed cytotoxic effect, with LC50 value of 8...
March 2018: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
Rehab M Abdel Megeed, Dalia B Fayed, Amira Abood, Mai O Kadry
Although, fluconazole is widely used in clinical treatment as an antifungal drug, it recorded potential problems as resistance and intracellular accumulation. Female albino mice were injected with single ip dose of Candida albicans (1.5 × 106 CFU) . Three weeks post treatment with fluconazole and two novel synthesized compounds [(2-(4-(Pyridin-2-yl) aminosulfonylphenylamino)-6-(naphthalen-2-yl)-4-(pyridin-2-yl) pyridine-3carbonitrile) and (2-(4-(Pyrimidin-2-yl) aminosulfonylphenylamino)-6-(naphthalen-2-yl)-4-(pyridine-2-yl)pyridine-3-carbonitrile) (13b & 14b, respectively)] in both low and high doses (50 mg/kg & 200 mg/kg), liver function and vaginal inflammation were assessed...
March 2018: Saudi Pharmaceutical Journal: SPJ: the Official Publication of the Saudi Pharmaceutical Society
Mariusz Z Ratajczak, Mateusz Adamiak, Monika Plonka, Ahmed Abdel-Latif, Janina Ratajczak
Hematopoietic stem/progenitor cells (HSPCs) circulate in peripheral blood (PB) under normal conditions and their number increases in response to stress, inflammation, tissue/organ injury, and may increase up to 100-fold after administration of mobilization-inducing drugs. Mounting evidence suggests that mobilizing agent-induced mobilization of HSPCs from bone marrow into PB is a result of innate immunity-mediated sterile inflammation in the bone marrow (BM) microenvironment. A critical initiating role in this process is played by tissue/organ injury-mediated or pharmacologically induced release from bone marrow-residing granulocytes and monocytes of (i) danger-associated molecular patterns (DAMPs), (ii) reactive oxygen species (ROS), and (iii) proteolytic and lipolytic enzymes...
March 5, 2018: Leukemia: Official Journal of the Leukemia Society of America, Leukemia Research Fund, U.K
Corinne Cayrol, Anais Duval, Pauline Schmitt, Stephane Roga, Mylène Camus, Alexandre Stella, Odile Burlet-Schiltz, Anne Gonzalez-de-Peredo, Jean-Philippe Girard
Allergic inflammation has crucial roles in allergic diseases such as asthma. It is therefore important to understand why and how the immune system responds to allergens. Here we found that full-length interleukin 33 (IL-33FL ), an alarmin cytokine with critical roles in type 2 immunity and asthma, functioned as a protease sensor that detected proteolytic activities associated with various environmental allergens across four kingdoms, including fungi, house dust mites, bacteria and pollens. When exposed to allergen proteases, IL-33FL was rapidly cleaved in its central 'sensor' domain, which led to activation of the production of type 2 cytokines in group 2 innate lymphoid cells...
March 19, 2018: Nature Immunology
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